人类复杂疾病相关的非编码区调控性单核苷酸变异预测研究

项目名称： 人类复杂疾病相关的非编码区调控性单核苷酸变异预测研究

项目编号： No.31301089

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 滕明祥

作者单位： 哈尔滨工业大学

项目金额： 22万元

中文摘要： 人类复杂疾病受基因组范围内多遗传位点、环境及其他因素的综合影响。广泛应用的复杂疾病遗传关联性研究手段有全基因组关联性分析（GWAS）与基因组重测序分析，其中GWAS以高效率、低花费的优点应用更为普遍。GWAS技术依赖于其他研究手段与方法帮助进一步确定疾病的确切致病性遗传位点，如昂贵的靶向测序技术或者生物信息学方法。针对单核苷酸变异，已有的生物信息学方法大多集中于注释可能影响蛋白质结构与功能的编码区位点；少数分析非编码区位点功能的方法要么无法考虑其潜在的调控机制，要么不能量化其调控功能大小。由于GWAS位点大多分布在非编码区域，且非编码区域占人类基因组约98%，本项目拟针对复杂疾病在非编码区的遗传关联性问题设计生物信息学方法，分析单核苷酸变异位点可能的转录调控、剪切调控与后转录调控机制，定量预测复杂疾病相关的调控性单核苷酸变异。该研究将推动复杂疾病的大规模遗传关联性分析，加速复杂疾病的研究。

中文关键词： 单核苷酸多态性；疾病表型；基因组数据资源；；

英文摘要： Human complex diseases are determined by multiple genetic loci, environment factors and other elements additively. The widely applied approaches to analyze genetic associations of complex diseases include genome wide association study (GWAS) and resequencing of individual genomes, while the former approach receives more acceptance with the advantages of high efficiency and low cost. GWAS experiments rely on other technologies or methods to detect the exact causal loci in diseases, such as the costly targeted sequencing technology or bioinformatics methods. For single nucleotide variations, most bioinformatics approaches aimed to annotate the coding region loci which may affect protein structures and functions; while a few approaches considering the non-coding region loci did not count either the regulatory mechanisms or the quantization of regulatory capability. Given the fact that most GWAS loci located in the non-coding region which accounted for 98% of human genome, this project will develop bioinformatics approaches applied in elucidating non-coding genetic association of complex diseases, to quantitatively analyze the potential regulatory mechanisms of single nucleotide variation in transcriptional regulation, splicing regulation and post-transcriptional regulation, targeting prediction of single nucleotide

英文关键词： Single Nucleotide Polymorphism；Disease Phenotypes；Genomic Data Sources；；